Selective C(sp3)-S Bond Cleavage of Thioethers to Build Up Unsymmetrical Disulfides

Ke Yang; Yanqi Luo; Qingyue Hu; Mengjie Song; Junxiang Liu; Zhengyi Li; Bijin Li; Xiaoqiang Sun

doi:10.1021/acs.joc.3c01355

Selective C(sp³)-S Bond Cleavage of Thioethers to Build Up Unsymmetrical Disulfides

J Org Chem. 2023 Oct 6;88(19):13699-13711. doi: 10.1021/acs.joc.3c01355. Epub 2023 Sep 25.

Authors

Ke Yang¹, Yanqi Luo¹, Qingyue Hu¹, Mengjie Song¹, Junxiang Liu², Zhengyi Li¹, Bijin Li², Xiaoqiang Sun¹

Affiliations

¹ Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou, Jiangsu 213164, China.
² Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.

PMID: 37747962
DOI: 10.1021/acs.joc.3c01355

Abstract

The selective C(sp³)-S bond cleavage of thioethers was first developed to prepare unsymmetrical disulfides by using electrophilic halogenation reagents. In this strategy, NBS (N-bromosuccinimide) achieves selective furfuryl C(sp³)-S bond cleavage of furfuryl alkylthioethers at room temperature. Meanwhile, NFSI (N-fluorobenzenesulfonimide) enables selective methyl C(sp³)-S bond cleavage of aryl and alkyl methylthioethers at an elevated temperature. Notably, the substrate scope investigation indicates that the order of selectivity of the C-S bond cleavage is furfuryl C(sp³)-S > benzyl C(sp³)-S > alkyl C(sp³)-S > C(sp²)-S bond. Moreover, this practical and operationally simple strategy also provides an important complementary way to access various unsymmetrical disulfides with excellent functional group tolerances and moderate to good yields.